The
investigational ritonavir-boosted protease inhibitor TMC310911 has a potent
antiviral effect, favourable pharmacokinetic profile and is safe and well-tolerated, according to results of a phase 2a clinical trial published in the
March 1 edition of the Journal of
Acquired Immune Deficiency Syndromes.

Four different
doses of the drug were evaluated, each showing a similar antiviral effect. The
study population consisted of 33 people who had not taken HIV treatment before (treatment-naive) and treatment
lasted for 14 days.

The findings build
on earlier research. Initial laboratory work showed that TMC310911 has activity
against both wild-type and drug-resistant strains of HIV. Evaluation of the
compound in a phase 1 study involving HIV-negative individuals suggested the
drug had good pharmacokinetics and was safe.

The latest
research was an open-label study involving people living with HIV who had never
taken antiretroviral treatment before. All the participants had fully
drug-sensitive virus.

The participants had a
median age of 32 years and 31 were white men. Almost two-thirds (64%) had a
baseline viral load between 10,000 and 100,000 copies/ml; the remaining participants
had a viral load above this level. The median duration of diagnosed HIV
infection was 2.7 years.

Participants were
randomised to receive one of four doses of TMC310911:

75mg twice daily.

150mg twice daily.

300mg twice daily.

300mg once daily.

All these doses
were taken with a 100mg ritonavir booster.

Treatment lasted
14 days.

A decrease in
viral load was observed after four days of therapy. On day eight, the mean declines
in viral load from baseline ranged between -1.30 log10 (75mg twice
daily) and -1.06 log10 (300mg
once daily). By day 15, falls in viral load from baseline were broadly similar
for all four doses and were between -1.79 log10 (150mg twice daily)
and -1.69 log10 (300mg twice daily).

All but one individual
had at least a 1 log10 fall in viral load. No participants developed
drug-resistant virus.

CD4 counts among people taking the once-daily 300mg dose increased by an average of 93
cells/mm3 between baseline and day 14. Modest falls in CD4 count
were observed in the other treatment arms.

Concentrations of
TMC310911 increased with dose. Daily exposure of the drug was comparable
between the 300mg once-daily dose and the 150mg twice-daily doses.

A total of 19 people experienced at least one treatment-associated side-effect. The most
common were mild tiredness (27%) and nausea (12%). No serious
treatment-associated adverse events were observed.

“The results of
this study further underline the antiviral potency of TMC310911 and provide the
first evidence of clinical efficacy of TMC310911,” comment the authors. “Efficacy,
safety, and PK [pharmacokinetic] findings from this study provide a strong basis for further
evaluation of TMC310911 in larger clinical trials of longer duration that may
include treatment-naive and treatment-experienced HIV-infected patients
carrying resistant virus.” The investigators recommend these studies should include
women and people with viral hepatitis and end-stage organ disease.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.